Reduced TIMP-2 in hypoxia enhances angiogenesis
| Autor: | Michal A. Rahat, Haim Bitterman, Lea Weiss-Cerem, Nitza Lahat, Miri Engelmayer-Goren, Doron Rosenzweig |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Sp1 Transcription Factor Physiology Angiogenesis Molecular Sequence Data Down-Regulation Neovascularization Physiologic Inflammation Biology Monocytes Cell Line Mice Cell Movement Internal medicine medicine Animals Humans Hypoxia Monocyte extravasation Cells Cultured Cell Proliferation Mice Inbred BALB C Tissue Inhibitor of Metalloproteinase-2 Base Sequence U937 cell Monocyte Endothelial Cells Cell Migration Inhibition U937 Cells Cell Biology Hypoxia (medical) Up-Regulation Cell biology Endothelial stem cell Endocrinology medicine.anatomical_structure medicine.symptom |
| Zdroj: | American Journal of Physiology-Cell Physiology. 300:C557-C566 |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | Hypoxia, which characterizes ischemia, trauma, inflammation, and solid tumors, recruits monocytes, immobilizes them, and alters their function, leading to an anti-inflammatory and proangiogenic phenotype. Monocyte extravasation from the circulation and their migration in tissues are partially mediated by the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The mechanisms evoked by hypoxia that regulate monocyte migration and activation are not entirely clear. Specifically, the effect of hypoxia on TIMPs in these cells has hardly been investigated. We show that hypoxia reduces TIMP-2 secretion from human primary monocytes and from the monocyte-like cell lines U937 and THP-1 by three- to fourfold ( P < 0.01), by inhibiting TIMP-2 transcription through mechanisms that involve the transcription factor SP-1. Hypoxia also lowers TIMP-2 protein secretion from human endothelial cells (by 2-fold, P < 0.05). TIMP-2 levels do not influence the reduced migration of THP-1 cells in hypoxia; however, low TIMP-2 levels enhance endothelial cell migration/proliferation, their ability to form tubelike structures in vitro, and the appearance of mature blood vessels in a Matrigel plug assay in vivo. Thus we conclude that reduced TIMP-2 levels secreted from both hypoxic monocytes and endothelial cells are proangiogenic. |
| Databáze: | OpenAIRE |
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